US10156520B2 - Array based sample characterization - Google Patents

Array based sample characterization Download PDF

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US10156520B2
US10156520B2 US14/787,953 US201414787953A US10156520B2 US 10156520 B2 US10156520 B2 US 10156520B2 US 201414787953 A US201414787953 A US 201414787953A US 10156520 B2 US10156520 B2 US 10156520B2
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sample
particles
illumination beam
sample holder
illumination
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US20160252453A1 (en
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E. Neil Lewis
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Malvern Panalytical Ltd
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
    • G01N21/53—Scattering, i.e. diffuse reflection within a body or fluid within a flowing fluid, e.g. smoke
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1429—Signal processing
    • G01N15/1433—Signal processing using image recognition
    • G01N15/1463—
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
    • G01N21/4133—Refractometers, e.g. differential
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
    • G01N21/6454—Individual samples arranged in a regular 2D-array, e.g. multiwell plates using an integrated detector array
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • G01N21/6458—Fluorescence microscopy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/061—Sources
    • G01N2201/06113—Coherent sources; lasers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/063—Illuminating optical parts
    • G01N2201/0636—Reflectors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/068—Optics, miscellaneous
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/12—Circuits of general importance; Signal processing

Definitions

  • This invention relates to methods and apparatus for detecting properties of samples, such as liquid samples, solid samples, solutions, slurries, and suspensions.
  • Lensless microfluidic detection techniques have been proposed to acquire microscopic images of samples such as biological materials and cells. They operate by acquiring images of suspended samples in close proximity to a high-resolution imaging detector. Their small size has resulted in their use being proposed in a variety of life science applications, including microscopes, smart petri dishes, and point-of-care diagnostic systems.
  • Systems according to the invention can help to inexpensively characterize small samples of a variety of different materials in different ways. These systems are applicable in research and industrial settings, such as in the development and manufacture of pharmaceuticals, personal care products, foodstuffs, pigments, and biomaterials, as well as in the areas of Metals, Mining, and Minerals (MMM). Their versatility and/or ability to characterize small samples can help to quickly develop materials and provide ongoing quality control and quality assurance in their handling and manufacture.
  • MMM Metals, Mining, and Minerals
  • FIG. 1 is a diagrammatic perspective view of a sample characterization system according to the invention that measures a refractive index of a sample
  • FIG. 2 is a diagrammatic perspective view of a sample characterization system according to the invention that measures a refractive index of multiple parts of a sample
  • FIG. 3 is a diagrammatic perspective view of a sample characterization system according to the invention that measures both the a refractive index and UV absorption of a sample
  • FIG. 4 is a diagrammatic perspective view of a sample characterization system according to the invention that measures both the a refractive index and UV absorption of multiple parts of a sample
  • FIG. 5 a is a diagrammatic perspective view of a sample characterization system according to the invention that measures both the a refractive index and multi-angle scattering characteristics of a sample
  • FIG. 5 b is a diagrammatic top view of the system of FIG. 5 a showing a first baffle position
  • FIG. 5 c is a diagrammatic top view of the system of FIG. 5 a showing a second baffle position
  • FIG. 6 a is a diagrammatic perspective view of a sample characterization system according to the invention that measures both the a refractive index and multi-angle scattering characteristics of different parts of a sample,
  • FIG. 6 b is a diagrammatic top view of the system of FIG. 6 a showing a first baffle position
  • FIG. 6 c is a diagrammatic top view of the system of FIG. 6 a showing a second baffle position
  • FIG. 7 is a diagrammatic elevation view of a moving mirror accessory for sample characterization system according to the invention that can excite different parts of a sample, such as different parts of a sample gradient,
  • FIG. 8 is a diagrammatic perspective view of a sample characterization system according to the invention that measures both the a refractive index and multi-angle scattering characteristics of a sample flowing through a flow cell,
  • FIG. 9 a is a diagrammatic perspective view of a sample characterization system according to the invention that measures both obscuration and deflection of a sample flowing through a narrow-channel flow cell,
  • FIG. 9 b is an illustrative histogram showing the frequency of observed particles for different refractive index ranges for the system of FIG. 9 a,
  • FIG. 10 is a set of five successive diagrammatic output images for the system of FIG. 9 ;
  • FIG. 11 is a diagrammatic perspective view of a sample characterization system according to the invention that measures multi-angle scattering using a reference beam
  • FIG. 12 is a diagrammatic perspective view of a sample characterization system according to the invention that measures a refractive index of a both a sample and a reference sample,
  • FIG. 13 is a diagrammatic block diagram of an embodiment of a high-throughput fluid characterization system according to the invention.
  • FIG. 14 is a diagrammatic top view of a three-detector sample characterization system according to the invention that measures both multi-angle scattering and UV absorption of a sample,
  • FIG. 15 is a diagrammatic top view of a three-detector sample characterization system according to the invention that measures multi-angle scattering, UV absorption, and viscosity of a sample, and
  • FIG. 16 is a diagrammatic perspective view of a sample characterization system according to the invention that uses an LED or broadband source and a laser line to measure absorption and scattering of a sample gradient.
  • a sample characterization system 10 characterizes a sample held in sample holder 12 . It includes an illumination source 15 , such as a laser positioned to shine its output radiation 16 toward the sample holder.
  • An illumination source 15 such as a laser positioned to shine its output radiation 16 toward the sample holder.
  • a two-dimensional array detector 14 is positioned at least generally opposite the test vessel from the laser.
  • Image analysis logic 18 is operatively connected to a data output of the two-dimensional array detector. This logic can be connected to and/or implemented using a computer 19 .
  • the two-dimensional array detector 14 can be any suitable type of array, such as such as a CCD or CMOS array detector. It can be a relatively high resolution array, such as one having a pixel pitch of under around 10 microns. In one embodiment, the array is implemented using a Sony 8MP smartphone camera chip. The color separation filters have been removed in this embodiment, but they can be used in other embodiments to detect light of different wavelengths.
  • Spectral filters can also be provided between the illumination source and the two-dimensional array detector, such as by depositing them on the array detector chip or as a separate element. These filters allow the system designer to filter out noise and/or focus on one or more wavelengths of interest. As is well known, these filters can be low-pass, high-pass, or band-pass filters, or combinations thereof. Linear variable filters can also be used in some embodiments to acquire measurements at several wavelengths.
  • the sample holder can hold a sample in a number of different ways.
  • the holder can be implemented as a cuvette, a capillary tube, a flow cell, a droplet holder or other suitable holder for a liquid sample.
  • the liquid sample holder is a square capillary tube.
  • the liquid sample can include one of a variety of types of liquids, such as solutions, slurries, dispersions, or suspensions.
  • the sample holder can also be configured to hold a solid sample, such as a crystal or a powder.
  • a solid sample such as a crystal or a powder.
  • This type of holder can be implemented in a variety of different ways, such as a platform, clamp, or powder vial. Gaseous samples can also be accommodated, such as in sealed vials.
  • the image analysis logic 18 can be implemented using special-purpose hardware, such as a dedicated image processing card and/or with one or more special-purpose software programs running on one or more general-purpose computer platforms 19 .
  • the computer can also control other functions of the instrument, such as turning the illumination source on and off and/or controlling the array detector.
  • these types of parts can be provided for each of the embodiments presented in the application.
  • illumination sources are used to produce beams shown in connection with the different embodiments.
  • the illumination source 15 illuminates the sample in the sample holder 12 with a sample output beam 16 .
  • the sample then refracts the beam by an amount related to its refractive index. This causes a resulting refracted beam to land at a position on the array along one or more of the axes that corresponds to the sample's refractive index.
  • the image analysis logic 18 can then calculate a value of the refractive index, such as by counting pixels and/or interpolating subpixels in one or more directions. Note that while the drawings show the x-direction as being horizontal, this and other embodiments can be constructed to detect deflection in other directions.
  • sample characterization system 20 characterizes a sample held in sample holder 12 at multiple places along the sample holder. It includes a plurality of illumination sources, such as lasers, positioned to shine their output beams 26 a . . . 26 n toward the .sample holder.
  • a two-dimensional array detector 24 is positioned at least generally opposite the test vessel from the lasers.
  • This embodiment differs from that shown in FIG. 1 in that the sample is illuminated at multiple different points along its length (y-axis). This allows readings for multiple sample points to be detected simultaneously.
  • This type of embodiment can allow measurements at different places on non-uniform samples, such as where a gradient exists in the fluid or where the fluid is flowing through the sample holder, such as from a liquid chromatography column. It may also allow averaging to take place to reduce the effect of unintended or undesirable heterogeneity in the sample.
  • a further embodiment of a sample characterization system 30 characterizes a sample held in sample holder 32 . It includes a first illumination source, such as a laser positioned to shine its output radiation 36 toward the sample holder, and second illumination source, such as an ultraviolet absorption source positioned to shine its output radiation 38 toward the sample holder.
  • a two-dimensional array detector 34 is positioned at least generally opposite the test vessel from the laser. Image analysis logic is operatively connected to a data output of the two-dimensional array detector.
  • the illumination source illuminates the sample in the sample holder 32 with a first sample output beam 36 .
  • the sample then causes the beam to refract by an amount related to its refractive index. This causes a resulting refracted beam to land at a position on the array along the x-axis that corresponds to the refractive index.
  • the image analysis logic 38 can then calculate the refractive index, such as by counting pixels and/or interpolating subpixels in the x-direction,
  • the system can also illuminate the sample with a second sample output beam 38 .
  • This beam is positioned to provide a transmission measurement, such as a UV transmission measurement.
  • the intensity of the beam received at the detector will therefore be indicative of the degree of absorption by the sample for the beam.
  • this measurement can be restricted to one or more spectral regions of interest.
  • the two types of measurements are performed during alternating periods in the present embodiment. It may be possible, however, to perform the measurements simultaneously in some circumstances.
  • FIG. 4 another embodiment of a sample characterization system 40 characterizes a sample held in sample holder 32 at multiple places along the sample holder. It includes a plurality of first illumination sources, such as lasers positioned to shine their output radiation beams 46 a . . . 46 n toward the sample holder. It also includes a plurality of second illumination sources, such as ultraviolet absorption sources positioned to shine their output radiation beams 48 toward the sample holder.
  • a two-dimensional array detector 44 is positioned at least generally opposite the test vessel from the laser. This embodiment differs from that shown in FIG. 3 in that sample is illuminated at multiple points different points along its length (y-axis). This allows two readings each for multiple sample points to be detected simultaneously.
  • a further embodiment of a sample characterization system 50 characterizes a sample held in sample holder 52 using two or more two-dimensional array detectors 54 a , 54 b .
  • the arrays are identical and are placed at right angles with respect to each along an upright edge, although other angles, orientations, and numbers of arrays can also be used, and different types of arrays can be mixed, such as arrays with different numbers of pixels, different pixel densities, or different spectral sensitivities.
  • the arrays form two sides of an incomplete cube, with the sample holder being placed generally in the center of the cube, but other configurations are also possible.
  • a beam 56 from an illumination source such as a laser is directed towards the sample holder, such as through an open side of the cube.
  • the illumination source illuminates the sample in the sample holder 52 with an output beam 56 .
  • the sample can then cause the beam to scatter in a manner that is related to the molecular weight of solutes and/or suspended particles in the sample. This generally causes scattered light to reach different parts of the array, with larger molecular weights scattering less uniformly, Image analysis logic can then calculate an effective molecular weight for the sample, such as by summing scattered light intensity from different angles detected at different locations and comparing the result to an incident beam intensity.
  • optical baffles can act as a zero-degree beam stop, or they can be used to prevent stray light, such as reflections from one measurement from affecting another.
  • FIGS. 6 a - c another embodiment of a sample characterization system 60 can .acquire samples from different parts of the sample holder. This embodiment differs from that of FIGS. 5 a -C that it allows an illumination beam 66 to illuminate the sample at different locations.
  • a plural beam generator 70 can be implemented using a movable mirror system 70 , which includes a mirror that can move parallel to the length of the sample holder 72 , while passing through different positions 74 a . . . 74 n .
  • the mirror can thus redirect a light beam 76 to different places along the sample holder.
  • Other methods of providing a synchronous or asynchronous plural beam generator can also be provided, such as using galvanometers or multiple sources.
  • a further embodiment of a sample characterization system 80 includes a flow cell 82 supplied by conduits 83 a , 83 b .
  • This allows measurements to be performed on flowing samples, such as the output of a liquid chromatography column, or a process feed.
  • the flow cell is shown in connection with a right-angle, laser-based multi-angle scattering setup, although it can be used in types of setups.
  • FIG. 9 another embodiment of a sample characterization system 90 according to the invention includes a narrow-channel flow cell 92 fed with .a flowing sample.
  • This flow cell can be placed in parallel with a two-dimensional array detector 94 , which is preferably a relatively high-speed detector.
  • a two-dimensional illumination beam 96 is then shone through the narrow-channel flow cell onto the array, preferably at least generally perpendicular to the direction of flow in the narrow-channel flow cell
  • the illumination beam can be produced in a variety of ways, such as by shining a laser through a cylindrical lens.
  • the two-dimensional illumination beam 96 produces a line image on the array (image 100 a ).
  • An opaque particle that then flows through the narrow-channel flow cell 92 will a obscure a portion of the beam 102 (image 100 b ).
  • the width of the obscuration of the beam will be related to a spatial dimension of the particle.
  • the duration of the obscuration of the beam will be related to a different spatial dimension of the particle.
  • a second, smaller particle, for example, might therefore produce another obscuration of a portion of the beam 104 , with this alteration being narrower and of shorter duration (image 100 c ).
  • a non-opaque, refracting particle refract a portion of the beam 106 by an amount related to its refractive index. This causes a resulting refracted portion of the beam to land at a position on the array that is offset along the y-axis (image 100 d ).
  • the extent of deflection will be related to the refractive index of the particle, and the width of the deflection will be related to the size of the particle.
  • Obscuring particles and refracting particles can be detected at the same time, resulting in an image with both offset 106 and obscured 108 beam portions (image 100 e ).
  • the image analysis logic can derive particle dimensions from the acquired images by converting the widths and durations associated with detected particles.
  • the image analysis logic can also derive an index of refraction for refracting particles. These results can then be stored, statistically analyzed, or otherwise processed and displayed, such as in the form of a histogram of numbers of observed particles against their refractive indices ( FIG. 9B ).
  • a further embodiment of a sample characterization system 110 includes a reference beam extractor 118 , such as a beam splitter, a bifurcated optical fiber, or an oscillating mirror.
  • This extractor produces a reference beam in addition to the sample beam, which is used to perform one or more measurements of characteristics of a sample in a sample holder 112 , such as its scattering characteristics. Both beams can then be imaged by one or more two-dimensional an-ay detectors 114 .
  • the use of a reference beam can improve sample characteristics detection, by providing a baseline to compare measurements against.
  • This baseline can compensate for a number of types of errors. For example, it can compensate for fluctuations or drift in the illumination source intensity, or in some embodiments it can provide information about the spectral content of the source before it is affected by interaction with the sample.
  • a sample characterization system 110 includes a reference beam extractor 129 , such as a beam splitter, a bifurcated optical fiber, or an oscillating mirror.
  • This extractor produces a reference beam in addition to the sample beam.
  • the sample beam is directed through a sample holder 122 a , to perform one or more measurements of characteristics of a sample, and the reference beam is directed through a reference sample holder. After interaction with the respective samples, both beams can be recorded by one or more two-dimensional array detectors 124 .
  • a reference sample can improve sample characteristics detection, by providing a baseline to compare measurements against.
  • This baseline can compensate for a number of types of errors. Like a baseline from a sample beam, it can compensate for fluctuations or drift in the illumination source intensity, or in some embodiments it can provide information about the spectral content of the source before it is affected by interaction with the sample. It can also allow a sample to be compared against a known standard, such as a known component of the sample.
  • an embodiment of a high-throughput fluid characterization system 40 uses a probe 135 to perform successive measurements on a number of liquid samples held in different vessels, such as wells 132 a 1 . . . 132 in of a multi-well plate 132 or carousel.
  • a negative/positive pressure drive 138 which can include a pump or other pressure source, is hydraulically connected to one or more capillary sipper tubes via a manifold.
  • the capillary tubes are positioned proximate one or more two-dimensional array detectors 132 and illuminated by one or more illumination sources.
  • the arrays and sources can be configured to perform any of the types of measurements presented in other embodiments of this application.
  • An off-the-shelf x-y-z stage is provided to successively position the samples under the probe, although other types of mechanisms can be used to position the vessels and probe relative to each other. Wash and waste vessels can also be provided, either in the plate, or separately.
  • the x-y-z stage begins by positioning a first of the wells below the probe to select a first sample.
  • This sample is drawn into the capillary tube, which acts as the sample holder, and a measurement is performed.
  • the sample can then returned to the vessel or discarded and the process repeated for another sample.
  • the process can be automated to run unattended.
  • a further embodiment of a sample characterization system 140 includes three two-dimensional array detectors 144 a , 144 b , 144 c , which are all oriented in the same y-direction but face inward in a spaced triangular configuration. In this case, they form an isosceles triangle with openings at each vertex. Inside the triangle is a sample holder 142 placed, in this case, at the center of mass of the triangle.
  • a first illumination source such as a laser, provides a first beam 146 a that is directed through the opening between the first two-dimensional array detector 144 a and the second two-dimensional array detector 144 b , toward the sample holder 142
  • a second illumination source such as a UV source, provides a second beam that is directed through the opening between the second two-dimensional array detector 144 b and the third two-dimensional array detector 1 44 c , toward the sample holder.
  • the two sources are switched or strobed such that they interact separately with the sample in the sample holder during successive sampling intervals, although it may also be possible in some embodiments to perform simultaneous measurements.
  • the first source excites the sample, and the resulting scattering is detected by one or more of the three two-dimensional array detectors 144 a , 144 b , 144 c . More specifically, the third two-dimensional array detector 144 c detects unscattered and low-angle forward-scattered radiation, and the first and second two-dimensional array detectors detect 90° and other high angle scattered radiation. The detected scattered radiation can then be analyzed by analysis logic. The sample can also refract the beam from the first source and the resulting deflection can be detected by the first two-dimensional detector 144 a . The second source illuminates the sample with UV radiation, and radiation that is not absorbed by the sample is transmitted to and detected by the first two-dimensional array detector 144 a.
  • FIG. 15 another embodiment of a sample characterization system 150 according to the invention includes three two-dimensional array detectors 154 a , 154 b , 154 c , which are all oriented in the same y-direction but face inward in a spaced triangular configuration. In this case they form an isosceles triangle with openings at each vertex. Inside the triangle is a sample holder 152 , which in this case is a capillary tube placed against the first two-dimensional array detector 154 a.
  • a first illumination source such as a laser, provides a first beam 156 a that is directed through the opening between the first two-dimensional array detector 154 a and the second two-dimensional array detector 154 b , toward the sample holder 152 .
  • a second illumination source such as a UV source, provides a second beam that is directed through the opening between the second two-dimensional array detector 144 b and the third two-dimensional array detector 144 c , toward the sample holder.
  • the two sources are switched or strobed such that they interact separately with the sample in the sample holder during successive sampling intervals, although it may also be possible in some embodiments to perform simultaneous measurements.
  • This embodiment differs from that described in connection with FIG. 14 in that it detects scattering according to a somewhat different geometry and further allows for the measurement of viscosity as described in U.S. application Ser. No. 13/844,951, filed Mar. 16, 2013 (now abandoned), Ser. No. 13/773,259, filed Feb. 21, 2013, Ser. No. 13/772,310, filed Feb. 20, 2013 (now abandoned), and Ser. No. 13/842,378, filed Mar. 15, 2013, which are all herein incorporated by reference.
  • U.S. application Ser. Nos. 13/884,951 and 13/772,310 were abandoned in favor of U.S. application Ser. No. 14/769,149, filed Aug. 20, 2015.
  • the first two-dimensional array detector also detects its viscosity by measuring how long it takes for a fluid meniscus to move through the capillary tube.
  • a further embodiment of a sample characterization system 160 includes a two-dimensional array detector 164 and a sample holder 162 , which in this case is a capillary tube placed proximate the two-dimensional array detector.
  • a first illumination source such as a laser equipped with a cylindrical lens, provides a first two-dimensional beam 166 a that is directed toward the sample holder 162 in a first direction that can be at least generally parallel to the plane of the two-dimensional array detector and along the longitudinal axis of the capillary tube.
  • a second illumination source such as a UV source, provides a second beam that is directed toward the sample holder, preferably at a different angle such as at a right angle with the detector.
  • the two sources are switched or strobed such that they interact separately with the sample in the sample holder during successive sampling intervals, although it may also be possible in some embodiments to perform simultaneous measurements.
  • the output beam of the first source causes scattering by the sample, which is detected by the array, and the output of the second source is partially transmitted through the sample, and detected by the array.
  • FIGS. 14 and 16 can be combined, for example, to measure a wide range of scattering angles for a sample in which a gradient exists.
  • other types of measurements such as Raman, IR, NIR, fluorescence, and reflectance measurements can be incorporated into the different embodiments and variants thereof.
  • Each of these measurements can be produced using a particular combination of source(s), filter(s), and/or detector(s).

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US20160252453A1 (en) 2016-09-01
EP3004843A2 (en) 2016-04-13
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CN105378458B (zh) 2021-05-25

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